methyl 8-(4-(18F)fluoranylanilino)-8-oxooctanoate | 1315344-79-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 8-(4-(18F)fluoranylanilino)-8-oxooctanoate
• CAS: 1315344-79-6
• 化学式: C₁₅H₂₀FNO₃
• 分子量: 280.329
• InChiKey: PXWVIJNSQFVJBW-GKTGUEEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 8-(4-(18F)fluoranylanilino)-8-oxooctanoate 在 羟胺 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 0.05h， 生成 4-(18)F-fluorosuberoylanilide hydroxamic acid
  参考文献：
  名称：

  In Vivo PET Imaging of Histone Deacetylases by ¹⁸F-Suberoylanilide Hydroxamic Acid (¹⁸F-SAHA)

  摘要：

  Histone deacetylases (HDACs) are a group of enzymes that modulate gene expression and cell state by deacetylation of both histone and non-histone proteins. A variety of HDAC inhibitors (HDACi) have already undergone clinical testing in cancer. Real-time in vivo imaging of HDACs and their inhibition would be invaluable; however, the development of appropriate imaging agents has remained a major challenge. Here, we describe the development and evaluation of F-18-suberoylanilide hydroxamic acid (F-18-SAHA 1a), a close analogue of the most clinically relevant HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). We demonstrate that 1a has near identical biochemical activity profiles to that of SAHA and report findings from pharmacokinetic studies. Using a murine ovarian. cancer model, we likewise show that HDAC inhibitor target binding efficacy can be quantitated within 24 h of administration. 1a thus represents the first F-18-positron emission tomography (PET) HDAC imaging agent, which also exhibits low nanomolar potency and is pharmacologically analogous to a clinically relevant HDAC inhibitor.

  DOI：

  10.1021/jm200620f
• 作为产物：
  描述：

  对二硝基苯 在 sodium tetrahydroborate 、 palladium 10% on activated carbon 、 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 作用下， 以 四氢呋喃 、 二甲基亚砜 、 乙腈 为溶剂， 反应 0.08h， 生成 methyl 8-(4-(18F)fluoranylanilino)-8-oxooctanoate
  参考文献：
  名称：

  In Vivo PET Imaging of Histone Deacetylases by ¹⁸F-Suberoylanilide Hydroxamic Acid (¹⁸F-SAHA)

  摘要：

  Histone deacetylases (HDACs) are a group of enzymes that modulate gene expression and cell state by deacetylation of both histone and non-histone proteins. A variety of HDAC inhibitors (HDACi) have already undergone clinical testing in cancer. Real-time in vivo imaging of HDACs and their inhibition would be invaluable; however, the development of appropriate imaging agents has remained a major challenge. Here, we describe the development and evaluation of F-18-suberoylanilide hydroxamic acid (F-18-SAHA 1a), a close analogue of the most clinically relevant HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). We demonstrate that 1a has near identical biochemical activity profiles to that of SAHA and report findings from pharmacokinetic studies. Using a murine ovarian. cancer model, we likewise show that HDAC inhibitor target binding efficacy can be quantitated within 24 h of administration. 1a thus represents the first F-18-positron emission tomography (PET) HDAC imaging agent, which also exhibits low nanomolar potency and is pharmacologically analogous to a clinically relevant HDAC inhibitor.

  DOI：

  10.1021/jm200620f

文献信息

• In Vivo PET Imaging of Histone Deacetylases by ¹⁸F-Suberoylanilide Hydroxamic Acid (¹⁸F-SAHA)
  作者：J. Adam Hendricks、Edmund J. Keliher、Brett Marinelli、Thomas Reiner、Ralph Weissleder、Ralph Mazitschek

  DOI：10.1021/jm200620f

  日期：2011.8.11

  Histone deacetylases (HDACs) are a group of enzymes that modulate gene expression and cell state by deacetylation of both histone and non-histone proteins. A variety of HDAC inhibitors (HDACi) have already undergone clinical testing in cancer. Real-time in vivo imaging of HDACs and their inhibition would be invaluable; however, the development of appropriate imaging agents has remained a major challenge. Here, we describe the development and evaluation of F-18-suberoylanilide hydroxamic acid (F-18-SAHA 1a), a close analogue of the most clinically relevant HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). We demonstrate that 1a has near identical biochemical activity profiles to that of SAHA and report findings from pharmacokinetic studies. Using a murine ovarian. cancer model, we likewise show that HDAC inhibitor target binding efficacy can be quantitated within 24 h of administration. 1a thus represents the first F-18-positron emission tomography (PET) HDAC imaging agent, which also exhibits low nanomolar potency and is pharmacologically analogous to a clinically relevant HDAC inhibitor.